Acceleration of Fracture Healing: a Comparison Between Clinical Available Low Intensity Pulsed Ultrasound (LIPUS) and a Novel BiModal Acoustic Signal System

Abstract

Ultrasound (US) accelerates healing by stimulating the production of bone callus and the process of mineralization. A US system (EXOGEN; Bioventus, Durham, NC, USA) using low intensity pulsed ultrasound (LIPUS) and this principle is FDA-approved. This study analyzed the effectiveness of a novel bimodal acoustic signal (BMAS) for bone fracture healing compared to the clinically used LIPUS system in an animal model. Seventeen mature white New Zealand female rabbits, underwent a bilateral fibula osteotomy as part of an IACUC-approved protocol. Afterwards, each rabbits’ legs were randomized to receive 20 minutes treatment daily for 18 days with BMAS or EXOGEN. The latter utilizes a longitudinal ultrasonic mode only, while the former employs US-induced shear stress to promote bone formation. Power Doppler imaging (PDI) was acquired days 0, 2, 4, 7, 11, 14 and 18 post-surgery to monitor treatment response and local inflammation. Images were analyzed off-line using ImageJ (NIH, Bethesda, MD, USA) for amount and intensity of flow. X-rays were acquired to evaluate fractures on days 0, 14, 18 and 21 post-surgery. Rabbits were euthanized day 21 post-surgery, the legs were extracted and their fibulas were analyzed with an electromechanical device to determine maximum torque, initial torsional stiffness and angular displacement at failure. The legs also underwent □ CT DEXA analysis to determine the ratio of bone mineral density (BMD) or bone mineral content (BMC) values at the fracture level over normal bone values. ANOVAs and paired t-tests were used to compare pairwise outcome variables for the 2 treatment modes on a per rabbit basis. The BMAS system induced better fracture healing with greater stiffness (0.042 ± 0.099 Ncm/deg, p = 0.050) and torque (1.574 ± 2.953 Ncm, p = 0.022) at the fracture sites than the LIPUS (EXOGEN) system. Quantitative PDI assessments showed a higher relative amount of vascularity (i.e., difference in pixel counts) with LIPUS (EXOGEN) than BMAS on days 4 and 18 (p 0.25. The novel BMAS technique achieved better bone fracture healing response than the current FDA-approved LIPUS (EXOGEN) system.